Palladium(II) Complexes of 4-Phenyl-3-thiosemicarbazone Ligands: Insights Into Cytotoxic Properties and Mode of Cell Death.

Reactions between sodium tetrachloropalladate and 2- (or 4-) substituted 4-phenyl-3-thiosemicarbazone ligands (HLR), with various electron-donating and electron-withdrawing substituents (R = OCH3, NO2, and Cl), afford square-planar complexes of the general formula [Pd(LR)2]. Ground-state geometry optimization and the vibrational analysis of cis- and trans-isomers of the complexes were carried out to get an insight into the stereochemistry of the complexes. Natural bond orbital analysis was used to analyze how the nature of the substituent affects the natural charge of the metal center, the type of hybridization, and the strength of the M-N and M-S bonds. Using spectrophotometry, the stability of the complexes, and their DNA binding abilities were assessed. The Pd(II) complexes showed moderate cytotoxicity against MCF-7 and Caco-2 cell lines, two of the assessed malignant cell lines, resulting in all known cell death types, including early apoptotic bodies and late apoptotic vacuoles as well as evident necrotic bodies.

Antimicrobial properties of triazolato terpyridine Pd(II) and Pt(II) complexes formed by [3+2] cycloaddition coupling reaction.

Modern classes of antimicrobials are crucial because most drugs in development today are basically antibiotic derivatives. Even though a large number of metal-based compounds have been studied as antimicrobial agents, relatively few studies have examined the antimicrobial properties of Pd(II) and Pt(II) compounds. The [3+2] cycloaddition reactions of [M(N3)L]PF6 (M = Pd(II) and Pt(II); L = 4'-(2-pyridyl)-2,2':6',2″-terpyridine) with 4,4,4-trifluoro-2-butynoic acid ethyl ester gave the corresponding triazolate complexes. The reaction products were fully characterized with a variety of analytical and spectroscopic tools including X-ray crystallographic analysis. The crystal structure of [Pd(triazolatoCF3,COOCH2CH3)L]PF6 provided cut-off evidence that the kinetically formed N1-triazolato isomer favoured the isomerization to the thermodynamically stable N2-analogue. The experimental work was complemented with computational work to get an insight into the nature of the predominant triazolate isomer. The lysozyme binding affinity of the triazolate complexes was examined by mass spectrometry. An analysis of the lysozyme Pd(II) adducts suggests a coordinative covalent mode of binding via the loss of the triazolato ligand. The free ligand and its triazolate complexes displayed selective toxicity against Candida albicans and Cryptococcus neoformans, while no cytotoxicity was observed against the normal human embryonic kidney cell line.

Role of the auxiliary ligand in determining the genotoxicity and mode of cell death of thiosemicarbazone Pd(II) complexes.

A series of Pd(II) complexes of the general formula [PdX(NNS)] (X = Cl, Br, I, NCS and phenyl-tetrazole-thiolato; NNS = 2-quinolinecarboxyaldehyde-N4-phenylthiosemicarbazone) was tested against four malignant cell lines for their antiproliferative properties and the outcomes were compared to those seen in normal mouse splenocytes. Various auxiliary ligands were substituted in order to investigate the impact of the character of the ligand on the cytotoxicity of this class of Pd(II) complexes. The iodo complex was the most cytotoxic compound towards the Caco-2 cell line in this study. The improved apoptosis and necrosis cell modes were in accordance with the fragmentation results of DNA, which revealed increased fragmentation terminals, especially in isothiocyanate and tetrazole-thiolato complexes. After 24 hours, at half the IC50 of each complex, the complex-treated cells exhibited considerable genotoxicity when compared to the corresponding non-treated control especially in the case of isothiocyanate and tetrazole-thiolato complexes.

Charge Transfer Copper Chelating Complex and Biogenically Synthesized Copper Oxide Nanoparticles Using Salvia officinalis Laves Extract in Comparative Spectrofluorimetric Estimation of Anticancer Dabrafenib.

Cancer is a broad category of disease that can affect virtually any organ or tissue in the body when abnormal cells grow uncontrollably, invade surrounding tissue, and/or spread to other organs. Dabrafenib is indicated for the treatment of adult patients with advanced non-small cell lung cancer. In the present study, two newly developed spectrofluorimetric probes for the detection of the anticancer drug Dabrafenib (DRF) in its authentic and pharmaceutical products using an ecologically synthesized copper oxide nanoparticle (CuONPs) from Salvia officinalis leaf extract and a copper chelate complex are presented. The first system is based on the influence of the particular optical properties of CuONPs on the enhancement of fluorescence detection. The second system, on the other hand, acts through the formation of a copper charge transfer complex. Various spectroscopic and microscopic studies were performed to confirm the environmentally synthesized CuONPs. The fluorescence detections in the two systems were measured at λex 350 and λem of 432 nm. The results showed the linear concentration ranges for the DRF-CuONPs-SDS and DRF-Cu-SDS complexes were determined to be 1.0-500 ng mL- 1 and 1.0-200 ng mL- 1, respectively. FI = 1.8088x + 21.418 (r = 0.9997) and FI = 2.7536x + 163.37 (r = 0.9989) were the regression equations. The lower detection and quantification limits for the aforementioned fluorescent systems were determined to be 0.4 and 0.8 ng mL- 1 and 1.0 ng mL- 1, respectively. The results also showed that intra-day DRF assays using DRF-CuONPs-SDS and DRF-Cu(NO3)2-SDS systems yielded 0.17% and 0.54%, respectively. However, the inter-day assay results for the above systems were 0.27% and 0.65%, respectively. The aforementioned two systems were effectively used in the study of DRF with excellent percent recoveries of 99.66 ± 0.42% and 99.42 ± 0.56%, respectively. Excipients such as magnesium stearate, titanium dioxide, red iron oxide, and silicon dioxide used in pharmaceutical formulations, as well as various common cations, amino acids, and sugars, had no effect on the detection of compound.

Reactivity of azido terpyridine Pd(ii) and Pt(ii) complexes towards 4,4,4-trifluoro-2-butynoic acid: structural insight into the triazolato coordination mode.

The mono- and binuclear azido terpyridine square-planar complexes of ionic formulas, [Pd2(N3)2L]2+ and [Pt(N3)L]+ (L = 1,4-bis(2,2':6',2''-terpyridin-4'yl)benzene), underwent the catalyst-free [3 + 2] cycloaddition coupling with 4,4,4-trifluoro-2-butynoic acid at ambient temperature affording the corresponding triazolate complexes. A mixture of triazolate isomers was generated by these inorganic click reactions. An increase in the solubility of the compounds was achieved by replacing the azido ligand with a triazolato ligand. By calculating the vibrational modes and comparing the total electronic and zero-point energy values, the local minimum structures of the complexes and the nature of the predominant triazolate isomer were verified. The theoretical work was complemented with natural bond analysis to get an insight into the natural charge and electronic arrangement of the metal ion, the hybridization of M-L bonds and strength of M-N bonds.

Ionophore-Based Polymeric Sensors for Potentiometric Assay of the Anticancer Drug Gemcitabine in Pharmaceutical Formulation: A Comparative Study.

Gemcitabine is a chemotherapeutic agent used to treat various malignancies, including breast and bladder cancer. In the current study, three innovative selective gemcitabine hydrochloride sensors are developed using 4-tert-butylcalix-[8]-arene (sensor 1), ß-cyclodextrin (sensor 2), and γ-cyclodextrin (sensor 3) as ionophores. The three sensors were prepared by incorporating the ionophores with o-nitrophenyl octyl ether as plasticizer and potassium tetrakis(4-chlorophenyl) borate as ionic additive into a polyvinyl chloride polymer matrix. These sensors are considered environmentally friendly systems in the analytical research. The linear responses of gemcitabine hydrochloride were in the concentration range of 6.0 × 10-6 to 1.0 × 10-2 mol L-1 and 9.0 × 10-6 to 1.0 × 10-2 mol L-1 and 8.0 × 10-6 to 1.0 × 10-2 mol L-1 for sensors 1, 2, and 3, respectively. Over the pH range of 6-9, fast-Nernst slopes of 52 ± 0.6, 56 ± 0.3, and 55 ± 0.8 mV/decade were found in the same order with correlation regressions of 0.998, 0.999, and 0.998, respectively. The lower limits of detection for the prepared sensors were 2.5 × 10-6, 2.2 × 10-6, and 2.7 × 10-6 mol L-1. The sensors showed high selectivity and sensitivity for gemcitabine. Validation of the sensors was carried out in accordance with the requirements established by the IUPAC, while being inexpensive and easy to use in drug formulation. A statistical analysis of the methods in comparison with the official method showed that there was no significant difference in accuracy or precision between them. It was shown that the new sensors could selectively and accurately find gemcitabine hydrochloride in bulk powder, pharmaceutical formulations, and quality control tests. The ionophore-based sensor shows several advantages over conventional PVC membrane sensor sensors regrading the lower limit of detection, and higher selectivity towards the target ion.

Synthesis of (R)-(6-Methoxyquinolin-4-yl)[(1S,2S,4S,5R)-5-vinylquinuclidin-2-yl]methanol Tetraphenylborate Ion-Pair Complex: Characterization, Antimicrobial, and Computational Study.

The (R)-(6-Methoxyquinolin-4-yl)[(1S,2S,4S,5R)-5-vinylquinuclidin-2-yl]methanol (quinine)-tetraphenylborate complex was synthesized by reacting sodium tetraphenyl borate with quinine in deionized water at room temperature through an ion-pair reaction (green chemistry) at room temperature. The solid complex was characterized by several physicochemical methods. The formation of ion-pair complex between bio-active molecules and/or organic molecules is crucial to comprehending the relationships between bioactive molecules and receptor interactions. The complex under study was examined for antimicrobial activity. All theoretical calculations were carried out in vacuum and water using the B3LYP level 6-311G(d,p) levels of theory. The theoretical computation allowed for the prediction and visualization of ionic interactions, which explained the complex's stability. The results of energy optimization showed that the Q-TPB complex is stable with a negative complexation energy. The obtained geometries showed that the boron (B-) and nitrogen (N+) in piperidine of the two molecules tetraphenylborate and quinine are close to each other, which makes it possible for ions to interact. The modest energy gap between HOMO and LUMO showed that the compound was stable. The computation of the electron transitions of the two models by density functional theory (TD-DFT) in the solvent at the theoretical level B3LYP/6-311G(d,p) allowed for the detection of three UV/visible absorption bands for both models and the discovery of a charge transfer between the host and the guest. The UV absorption, infrared, and H NMR are comparable with the experimental part.

Evaluation of Alectinib Metabolic Stability in HLMs Using Fast LC-MS/MS Method: In Silico ADME Profile, P450 Metabolic Lability, and Toxic Alerts Screening.

Alectinib, also known as Alecensa®, is prescribed for the therapeutic treatment of individuals diagnosed with metastatic non-small cell lung cancer (NSCLC) who have a specific genetic mutation referred to as anaplastic lymphoma kinase (ALK) positivity. The Food and Drug Administration granted regular approval to alectinib, a drug developed by Hoffmann-La Roche, Inc. (Basel, Switzerland)/Genentech, Inc. (South San Francisco, CA, USA), on 6 November 2017. The screening of the metabolic stability and identification of hazardous alarms within the chemical structure of ALC was conducted using the StarDrop software package (version 6.6), which incorporates the P450 metabolic module and DEREK software (KB 2018 1.1). The primary aim of this investigation was to develop a high-throughput and accurate LC-MS/MS technique for the quantification of ALC in the metabolic matrix (human liver microsomes; HLMs). The aforementioned methodology was subsequently employed to assess the metabolic stability of ALC in HLMs through in vitro tests, with the obtained results further validated using in silico software. The calibration curve of the ALC showed a linear correlation that exists within the concentration range from 1 to 3000 ng/mL. The LC-MS/MS approach that was recommended exhibited accuracy and precision levels for both inter-day and intra-day measurements. Specifically, the accuracy values ranged from -2.56% to 3.45%, while the precision values ranged from -3.78% to 4.33%. The sensitivity of the established approach was proved by its ability to adhere to an LLOQ of 0.82 ng/mL. The half-life (t1/2) and intrinsic clearance (Clint) of ALC were estimated to be 22.28 min and 36.37 mL/min/kg, correspondingly, using in vitro experiments. The ALC exhibited a moderate extraction ratio. The metabolic stability and safety properties of newly created derivatives can be enhanced by making modest adjustments to the morpholine and piperidine rings or by substituting the substituent, as per computational software. In in silico ADME prediction, ALC was shown to have poor water solubility and high gastrointestinal absorption along with inhibition of some cytochrome P450s (CYP2C19 and CYP2C9) without inhibition of others (CYP1A2, CYP3A4, and CYP2D6) and P-glycoprotein substrate. The study design that involves using both laboratory experiments and different in silico software demonstrates a novel and groundbreaking approach in the establishment and uniformization of LC-MS/MS techniques for the estimation of ALC concentrations, identifying structural alerts and the assessment of its metabolic stability. The utilization of this study strategy has the potential to be employed in the screening and optimization of prospective compounds during the drug creation process. This strategy may also facilitate the development of novel derivatives of the medicine that maintain the same biological action by targeted structural modifications, based on an understanding of the structural alerts included within the chemical structure of ALC.

Fabrication and Applications of Potentiometric Membrane Sensors Based on Specific Recognition Sites for the Measurement of the Quinolone Antibacterial Drug Gemifloxacin.

Supramolecular gemifloxacin (GF) sensors have been developed. Supramolecular chemistry is primarily concerned with noncovalent intermolecular and intramolecular interactions, which are far weaker than covalent connections, but they can be exploited to develop sensors with remarkable affinity for a target analyte. In order to determine the dose form of the quinolone antibacterial drug gemifloxacin, the current study's goal is to adapt three polyvinylchloride (PVC) membrane sensors into an electrochemical technique. Three new potentiometric membrane sensors with cylindric form and responsive to gemifloxacin (GF) were developed. The sensors' setup is based on the usage of o-nitrophenyl octyl ether (o-NPOE) as a plasticizer in a PVC matrix, ß-cyclodextrin (ß-CD) (sensor 1), γ-cyclodextrin (γ-CD) (sensor 2), and 4-tert-butylcalix[8]arene (calixarene) (sensor 3) as an ionophore, potassium tetrakis (4-chlorophenyl) borate (KTpClPB) as an ion additive for determination of GF. The developed method was verified according to IUPAC guidelines. The sensors under examination have good selectivity for GF, according to their selectivity coefficients. The constructed sensors demonstrated a significant response towards to GF over a concentration range of 2.4 × 10-6, 2.7 × 10-6, and 2.42 × 10-6 mol L-1 for sensors 1, 2, and 3, respectively. The sensors showed near-Nernstian cationic response for GF at 55 mV, 56 mV, and 60 mV per decade for sensors 1, 2, and 3, respectively. Good recovery and relative standard deviations during the day and between days are displayed by the sensors. They demonstrated good stability, quick response times, long lives, rapid recovery, and precision while also exhibiting good selectivity for GF in various matrices. To determine GF in bulk and dose form, the developed sensors have been successfully deployed. The sensors were also employed as end-point indicators for titrating GF with sodium tetraphenyl borate.

Fabrication and Applications of Potentiometric Membrane Sensors Based on γ-Cyclodextrin and Calixarene as Ionophores for the Determination of a Histamine H1-Receptor Antagonist: Fexofenadine.

Supramolecular fexofenadine sensors have been constructed. Although noncovalent intermolecular and intramolecular interactions, which are far weaker than covalent contacts, are the main focus of supramolecular chemistry, they can be used to create sensors with an exceptional affinity for a target analyte. The objective of the current research study is to adapt two PVC membrane sensors into an electrochemical approach for the dosage form determination of histamine H1-receptor antagonists: fexofenadine. The general performance characteristics of two new modified potentiometric membrane sensors responsive to fexofenadine hydrochloride were established. The technique was based on the employment of γ-cyclodextrin (CD) (sensor 1), 4-tert-butylcalix[8]arene (calixarene) (sensor 2) as an ionophore, potassium tetrakis (4-chlorophenyl) borate (KTpClPB) as an ion additive, and (o-NPOE) as a plasticizer for sensors 1 and 2. The sensors showed fast responses over a wide fexofenadine concentration range (1 × 10-2 to 4.5 (4.7) × 10-6 M), with detection limits of 1.3 × 10-6 M and 1.4 × 10-6 M for sensors 1 and 2, respectively, in the pH range of 2-8. The tested sensors exhibit the fexofenadine near-Nernstian cationic response at 56 and 58 mV/decade for sensors 1 and 2, respectively. The sensors exhibit good stability, fast response times, accuracy, precision, and longer life for fexofenadine. Throughout the day and between days, the sensors exhibit good recovery and low relative standard deviations. Fexofenadine in its pure, dose form has been identified with success using the modified sensors. The sensors were employed as end-point indications for the titration of fexofenadine with NaTPB.

In vitro cytotoxicity of Mn(I) and Ru(II) carbonyls with a diphenyl pyridyl phosphine coligand towards leukaemia.

Human acute monocytic leukaemia cells were tested under both dark and light conditions for their susceptibility to Mn(I) and Ru(II) carbonyl complexes with a diphenyl pyridyl phosphine coligand. The Ru(II) complex (IC50 = 7.13 ± 0.8 µM) displayed higher outstanding potency against leukaemia than the Mn(I) analogue (54.58 ± 4.1 µM) in the dark and both complexes were completely harmless to healthy mouse bone marrow cells.

Biological Investigation of 2-Thioxo-benzo[g]quinazolines against Adenovirus Type 7 and Bacteriophage Phi X174: An In Vitro Study.

Mortality and morbidity caused by viruses are a global health problems. Therefore, there is always a need to create novel therapeutic agents and refine existing ones to maximize their efficacy. Our lab has produced benzoquinazolines derivatives that have proven effective activity as antiviral compounds against herpes simplex (HSV 1 and 2), coxsackievirus B4 (CVB4), and hepatitis viruses (HAV and HCV). This in vitro study was aimed at investigating the effectiveness of benzoquinazoline derivatives 1-16 against adenovirus type 7 and bacteriophage phiX174 using a plaque assay. The cytotoxicity against adenovirus type 7 was also performed in vitro, using a MTT assay. Most of the compounds exhibited antiviral activity against bacteriophage phiX174. However, compounds 1, 3, 9, and 11 showed statistically significant reductions of 60-70% against bacteriophage phiX174. By contrast, compounds 3, 5, 7, 12, 13, and 15 were ineffective against adenovirus type 7, and compounds 6 and 16 had remarkable efficacy (50%). Using the MOE-Site Finder Module, a docking study was carried out in order to create a prediction regarding the orientation of the lead compounds (1, 9, and 11). This was performed in order to investigate the activity of the lead compounds 1, 9, and 11 against the bacteriophage phiX174 by locating the ligand-target protein binding interaction active sites.

Benzo[g]quinazolines as antifungal against candidiasis: Screening, molecular docking, and QSAR investigations.

Candida albicans, an opportunistic pathogen, is the most common type of fungus and represents a substantial source of human invasive disease (nosocomial infection). This category of fungi are part of our microbiota, and given the appropriate environmental conditions, it has the potential to cause both superficial and systemic infections. There is a soaring resistance against the available anticandidal agents. The purpose of this research is to investigate the activity of certain previously synthesized benzo[g]quinazolines against C. albicans in vitro by using the cup-plate diffusion method. There was a marked difference in the effectiveness of the target compounds 1-6 against the sample of C. albicans that was tested. Benzo[g]quinazolines 1 (inhibition zone = 20 mm) and 2 (inhibition zone = 22 mm) had good effects in comparison to fluconazole (inhibition zone = 26 mm). A docking study was conducted between benzo[g]quinazolines 1-6 and Candida spp. CYP51 to establish the binding mode compared with fluconazole and VT-1161 (oteseconazole) as reference medicines, and it was determined that binding at the active site of Candida spp. CYP51 occurred in the same manner. Quantitative structure-activity relationship (QSAR) investigation was performed to further characterize the identified anticandidal agents and recognize the major regulatory components governing such activity. In future studies, the benzo[g]quinazoline scaffold could serve as a model for the design and development of novel derivatives with antifungal potential.

Antiviral activity of some benzo[g]quinazolines against coxsackievirus B4: biological screening and docking study.

BACKGROUND: Serotype coxsackievirus B (CVB) infection has been linked to viral myocarditis, dilated cardiomyopathy, meningitis, and pancreatitis in children and young adults. As of yet, no antiviral drug has been authorized for the treatment of coxsackievirus infection. Therefore, there is perpetual demand for new therapeutic agents and the improvement of existing ones. Benzo[g]quinazolines, the subject of several well-known heterocyclic systems, have risen to prominence and played a significant role in the development of antiviral agents, particularly those for anti-coxsackievirus B4 infection. METHODS: This study investigated the cytotoxicity of the target benzo[g]quinazolines (1-16) in the BGM cells line as well as their anti-coxsackievirus B4 activity. Determination of CVB4 titers using a plaque assay. RESULTS: Most of the target benzoquinazolines exhibited antiviral activity, however, compounds 1-3 appeared to be the most effective (reduction percentages of 66.7, 70, and 83.3%, respectively). The binding mechanisms and interactions of the three most active 1-3 with the constitutive amino acids in the active site of the multi-target of coxsackievirus B4 (3Clpro and RdRp) targets were also investigated using molecular docking. CONCLUSION: The anti coxsackievirus B4 activity has resulted, and the top three active benzoquinazolines (1-3) have bonded to and interacted with the constitutive amino acids in the active region of the multi-target coxsackievirus B4 (RdRp and 3Clpro). Further research is required in the lab. to determine the exact benzoquinazolines mechanism of action.

Assessment of In Silico and In Vitro Selpercatinib Metabolic Stability in Human Liver Microsomes Using a Validated LC-MS/MS Method.

Selpercatinib (SLP; brand name Retevmo®) is a selective and potent RE arranged during transfection (RET) inhibitor. On 21 September 2022, the FDA granted regular approval to SLP (Retevmo, Eli Lilly, and Company). It is considered the only and first RET inhibitor for adults with metastatic or locally advanced solid tumors with RET gene fusion. In the current experiment, a highly specific, sensitive, and fast liquid chromatography tandem mass spectrometry (LC-MS/MS) method for quantifying SLP in human liver microsomes (HLMs) was developed and applied to the metabolic stability evaluation of SLP. The LC-MS/MS method was validated following the bioanalytical methodology validation guidelines outlined by the FDA (linearity, selectivity, matrix effect, accuracy, precision, carryover, and extraction recovery). SLP was detected by a triple quadrupole detector (TQD) using a positive ESI source and multiple reaction monitoring (MRM) mode for mass spectrometric analysis and estimation of analytes ions. The IS-normalized matrix effect and extraction recovery were acceptable according to the FDA guidelines for the bioanalysis of SLP. The SLP calibration standards were linear from 1 to 3000 ng/mL HLMs matrix, with a regression equation (y = 1.7298x + 3.62941) and coefficient of variation (r2 = 0.9949). The intra-batch and inter-batch precision and accuracy of the developed LC-MS/MS method were -6.56-5.22% and 5.08-3.15%, respectively. SLP and filgotinib (FLG) (internal standard; IS) were chromatographically separated using a Luna 3 µm PFP (2) stationary phase (150 × 4.6 mm) with an isocratic mobile phase at 23 ± 1 °C. The limit of quantification (LOQ) was 0.78 ng/mL, revealing the LC-MS/MS method sensitivity. The intrinsic clearance and in vitro t1/2 (metabolic stability) of SLP in the HLMs matrix were 34 mL/min/kg and 23.82 min, respectively, which proposed an intermediate metabolic clearance rate of SLP, confirming the great value of this type of kinetic experiment for more accurate metabolic stability predictions. The literature review approved that the established LC-MS/MS method is the first developed and reported method for quantifying SLP metabolic stability.

Prospective of Agro-Waste Husks for Biogenic Synthesis of Polymeric-Based CeO2/NiO Nanocomposite Sensor for Determination of Mebeverine Hydrochloride.

BACKGROUND: The remarkable properties of nickel oxide (NiO) and cerium oxide (CeO2) nanostructures have attracted considerable interest in these nanocomposites as potential electroactive materials for sensor construction. METHODS: The mebeverine hydrochloride (MBHCl) content of commercial formulations was determined in this study using a unique factionalized CeO2/NiO-nanocomposite-coated membrane sensor. RESULTS: Mebeverine-phosphotungstate (MB-PT) was prepared by adding phosphotungstic acid to mebeverine hydrochloride and mixing with a polymeric matrix (polyvinyl chloride, PVC) and plasticizing agent o-nitrophenyl octyl ether. The new suggested sensor showed an excellent linear detection range of the selected analyte at 1.0 × 10-8-1.0 × 10-2 mol L-1 with regression equation EmV = (-29.429 ± 0.2) log [MB] + 347.86. However, the unfunctionalized sensor MB-PT displayed less linearity at 1.0 × 10-5-1.0 × 10-2 mol L-1 drug solution with regression equation EmV = (-26.603 ± 0.5) log [MB] + 256.81. By considering a number of factors, the applicability and validity of the suggested potentiometric system were improved following the rules of analytical methodological requirements. CONCLUSION: The created potentiometric technique worked well for determining MB in bulk substance and in medical commercial samples.

Synthesis of 4-Amino-N-[2 (diethylamino)Ethyl]Benzamide Tetraphenylborate Ion-Associate Complex: Characterization, Antibacterial and Computational Study.

The 4-amino-N-[2 (diethylamino) ethyl] benzamide (procainamide)-tetraphenylborate complex was synthesized by reacting sodium tetraphenyl borate with 4-amino-N-[2 (diethylamino) ethyl] benzamide, chloride salt, and procainamide in deionized water at room temperature through an ion-associate reaction (green chemistry) at room temperature, and characterized by several physicochemical methods. The formation of ion-associate complex between bio-active molecules and/or organic molecules is crucial to comprehending the relationships between bioactive molecules and receptor interactions. The solid complex was characterized by infrared spectra, NMR, elemental analysis, and mass spectrometry, indicating the formation of ion-associate or ion-pair complex. The complex under study was examined for antibacterial activity. The ground state electronic characteristics of the S1 and S2 complex configurations were computed using the density functional theory (DFT) approach, using B3LYP level 6-311 G(d,p) basis sets. R2 = 0.9765 and 0.9556, respectively, indicate a strong correlation between the observed and theoretical 1H-NMR, and the relative error of vibrational frequencies for both configurations was acceptable, as well. HOMO and LUMO frontier molecular orbitals and molecular electrostatics using the optimized were used to obtain a potential map of the chemical. The n → π* UV absorption peak of the UV cutoff edge was detected for both configurations of the complex. Spectroscopic methods were structures used to characterize the structure (FT-IR and 1HNMR). In the ground state, DFT/B3LYP/6-311G(d,p) basis sets were used to determine the electrical and geometric properties of the S1 and S2 configurations of the title complex. Comparing the observed and calculated values for the S1 and S2 forms, the HOMO-LUMO energy gap of compounds was 3182 and 3231 eV, respectively. The small energy gap between HOMO and LUMO indicated that the compound was stable. In addition, the MEP reveals that positive potential sites were around the PR molecule, whereas negative potential sites were surrounding the TPB site of atoms. The UV absorption of both arrangements is comparable to the experimental UV spectrum.

Development of an LC-MS/MS Method for Quantification of Sapitinib in Human Liver Microsomes: In Silico and In Vitro Metabolic Stability Evaluation.

Sapitinib (AZD8931, SPT) is a tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR) family (pan-erbB). In multiple tumor cell lines, STP has been shown to be a much more potent inhibitor of EGF-driven cellular proliferation than gefitinib. In the current study, a highly sensitive, rapid, and specific LC-MS/MS analytical method for the estimation of SPT in human liver microsomes (HLMs) was established with application to metabolic stability assessment. The LC-MS/MS analytical method was validated in terms of linearity, selectivity, precision, accuracy, matrix effect, extraction recovery, carryover, and stability following the FDA guidelines for bioanalytical method validation. SPT was detected using electrospray ionization (ESI) as an ionization source under multiple reaction monitoring (MRM) in the positive ion mode. The IS-normalized matrix factor and extraction recovery were acceptable for the bioanalysis of SPT. The SPT calibration curve was linear, from 1 ng/mL to 3000 ng/mL HLM matrix samples, with a linear regression equation of y = 1.7298x + 3.62941 (r2 = 0.9949). The intraday and interday accuracy and precision values of the LC-MS/MS method were -1.45-7.25% and 0.29-6.31%, respectively. SPT and filgotinib (FGT) (internal standard; IS) were separated through the use of an isocratic mobile phase system with a Luna 3 µm PFP(2) column (150 × 4.6 mm) stationary phase column. The limit of quantification (LOQ) was 0.88 ng/mL, confirming the LC-MS/MS method sensitivity. The intrinsic clearance and in vitro half-life of STP were 38.48 mL/min/kg and 21.07 min, respectively. STP exhibited a moderate extraction ratio that revealed good bioavailability. The literature review demonstrated that the current analytical method is the first developed LC-MS/MS method for the quantification of SPT in an HLM matrix with application to SPT metabolic stability evaluation.

Evaluation of Some Benzo[g]Quinazoline Derivatives as Antiviral Agents against Human Rotavirus Wa Strain: Biological Screening and Docking Study.

Globally, rotavirus (RV) is the most common cause of acute gastroenteritis in infants and toddlers; however, there are currently no agents available that are tailored to treat rotavirus infection in particular. Improved and widespread immunization programs are being implemented worldwide to reduce rotavirus morbidity and mortality. Despite certain immunizations, there are no licensed antivirals that can attack rotavirus in hosts. Benzoquinazolines, chemical components synthesized in our laboratory, were developed as antiviral agents, and showed good activity against herpes simplex, coxsackievirus B4 and hepatitis A and C. In this research project, an in vitro investigation of the effectiveness of benzoquinazoline derivatives 1-16 against human rotavirus Wa strains was carried out. All compounds exhibited antiviral activity, however compounds 1-3, 9 and 16 showed the greatest activity (reduction percentages ranged from 50 to 66%). In-silico molecular docking of highly active compounds, which were selected after studying the biological activity of all investigated of benzo[g]quinazolines compounds, was implemented into the protein's putative binding site to establish an optimal orientation for binding. As a result, compounds 1, 3, 9, and 16 are promising anti-rotavirus Wa strains that lead with Outer Capsid protein VP4 inhibition.

Atropine-Phosphotungestate Polymeric-Based Metal Oxide Nanoparticles for Potentiometric Detection in Pharmaceutical Dosage Forms.

The new research presents highly conductive polymeric membranes with a large surface area to volume ratio of metal oxide nanoparticles that were used to determine atropine sulfate (AT) in commercial dosage forms. In sensing and biosensing applications, the nanomaterials zinc oxide (ZnONPs) and magnesium oxide (MgONPs) were employed as boosting potential electroactive materials. The electroactive atropine phosphotungstate (AT-PT) was created by combining atropine sulfate and phosphotungstic acid (PTA) and mixing it with polymeric polyvinyl chloride (PVC) with the plasticizer o-nitrophenyl octyl ether (o-NPOE). The modified sensors AT-PT-ZnONPs or AT-PT-MgONPs showed excellent selectivity and sensitivity for the measurements of atropine with a linear concentration range of 6.0 × 10-8 - 1.0 × 10-3 and 8.0 × 10-8 - 1.0 × 10-3 mol L-1 with regression equations of E(mV) = (56 ± 0.5) log [AT] - 294 and E(mV) = (54 ± 0.5) log [AT] - 422 for AT-PT-NPs or AT-PT-MgONPs sensors, respectively. The AT-PT coated wire sensor, on the other hand, showed a Nernstian response at 4.0 × 10-6 - 1.0 × 10-3 mol L-1 and a regression equation E(mV) = (52.1 ± 0.2) log [AT] + 198. The methodology-recommended guidelines were used to validate the suggested modified potentiometric systems against various criteria.